FATTY-ACID - MEDIATED EFFECTS ON THE GLUTATHIONE REDOX CYCLE IN CULTURED ENDOTHELIAL-CELLS

Endothelial barrier dysfunction after exposure to fatty acids may be m ediated by disturbances in antioxidant protection. To evaluate this hy pothesis, components of the glutathione redox cycle such as total, red uced, and oxidized glutathione and glutathione reductase and peroxidas e were measured in cultured porcine endothelial cells exposed to 90 mu mol/L of stearic acid (18:0), oleic acid (18:1 omega-9), linoleic aci d (18:2 omega-6), linolenic acid (18:3 omega-3), and/or buthionine sul foximine (BSO). Treatment with fatty acids caused an initial decrease in glutathione concentrations, which was followed by an increase at la ter time points. The most marked changes in glutathione redox cycle co mponents were induced by 18:2. BSO increased susceptibility of fatty a cid-mediated injury to endothelial monolayers. The results indicate a fundamental role of the glutathione redox cycle in protection against fatty acid-mediated injury to the vascular endothelium.